The genetic understanding of cancer has led to enhanced individual risk assessment, improved screening guidelines, and improved outcomes based on cancer prevention, early detection, and, in some cases, targeted therapy. Huntsman Cancer Institute (HCI) is positioned to make exceptional contributions in this individualized oncology arena. HCI has a unique research resource to support genetic and population studies, the Utah Population Database (UPDB), a compelling history of genetic discovery in oncology, and a strategic plan to accelerate translational advances from this platform. We have forged an alliance with Intermountain Healthcare, a nationally acclaimed Utah health network, linking data for more than 80-85 percent of the cancer patients in our State to the UPDB, enabling the entire population of Utah to comprise a cancer research laboratory for genetic, population, and outcomes research. Utah is home to seven Native American tribes or nations as well as extensive rural and frontier populations that have poor cancer outcomes. We aim to serve as a national research resource for addressing the needs of these underserved populations to improve cancer prevention and care. HCI research is organized into five Programs that provide an environment of cancer focus, transdisciplinary exchange, and collaboration: Nuclear Control of Cell Growth and Differentiation; Cell Response and Regulation; Imaging, Diagnostics, and Therapeutics; Gastrointestinal Cancers; and Cancer Control and Population Sciences. These Programs integrate the activities of 133 members who have $45 million in extramural grant support, with more than $17 million in NCI direct costs. Cancer-focused research during the current award period is documented in 1,374 unique publications, of which 26 percent are collaborative with one or more Cancer Center members. Thirteen Cancer Center Shared Resources support our scientists, providing access to specialized instrumentation, assays, services, research materials, and expert consultation and collaboration. We request funds to support Years 21-25 of our Cancer Center Support Grant (CCSG). A new Executive Director, Mary Beckerle, Ph.D., was appointed in August 2006. Under her leadership, HCI has developed a plan to guide the next five years, including expansion of HCI's cancer specialty hospital, expansion of HCI's genetic platform for pre-clinical studies, development of a Center for Investigational Therapeutics (including a Phase I program), and expansion of population science (including epidemiological and behavioral research) to impact care of cancer survivors and reduce health disparities.